hedgehog pathway inhibitor

RU-SKI 43 is a potent and selective hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. It exhibits anticancer activity and is a potential treatment for lung adenocarcinomas. RU-SKI 43 reduces Gli-1 activation through smoothening-independent non-canonical signaling and inhibits Akt and mTOR pathway activity.

CUR61414 is a cell-permeable inhibitor of Hedgehog signaling pathway (IC50 =100-200 nM) and selectively binds to smoothened (Ki = 44 nM).

CUR61414 hydrochloride is a potent and cell permeable inhibitor of Hedgehog signaling pathway (IC50 =100-200 nM). CUR61414 hydrochloride is a small-molecule aminoproline class compound. CUR61414 hydrochloride selectively binds to smoothened (Smo, Ki= 44 nM). CUR61414 hydrochloride can induce cancer cells apoptosis without affecting neighboring non-tumor cells.

LGE-899 (Sonidegib metabolite M48) is a main metabolite of Sonidegib which is an inhibitor of the hedgehog pathway. The Tmax of LGE-899(60 h) is much longer than Sonidegib.

Itraconazole (R51211) is a triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes necessary for ERGOSTEROL synthesis.

Vismodegib (GDC-0449) is a hedgehog pathway inhibitor (IC50: 3 nM). It also inhibits P-gp (IC50: 3.0 μM), ABCG2 (IC50: 1.4 μM).

HhAntag is a small molecule inhibitor of GLI1-mediated transcription, an essential down-stream element of the Hedgehog (Hh) pathway with the anti-tumor activity.

Saridegib is an effective and specific inhibitor of Smoothened and a key signaling transmembrane protein in the Hedgehog pathway.

HedgehogIN-7 (Compound 8g), a purine derivative, acts as an inhibitor of the Hedgehog signaling pathway by reducing the expression of Hedgehog genes and inhibiting signal transmission. This compound exhibits significant cytotoxicity and selectivity towards Mia-PaCa-2 pancreatic cancer cells that are dependent on the Hedgehog pathway, making it useful for research in pancreatic cancer.

SMO-IN-5 (Compound 25(B31)) is an effective inhibitor of smoothened (SMO), which suppresses the Hedgehog (Hh) signaling pathway. This compound inhibits cellular proliferation and induces apoptosis, demonstrating antitumor activity.

HPI 1 is a hedgehog (Hh) signaling inhibitor. Inhibits Sonic hedgehog (Shh)-, SAG- and Gli-induced Hh pathway activation in Shh-LIGHT2 cells (IC50 values are 1.5, 1.5, 4, and 6 μM for Shh-, SAG-, Gli2- and Gli1-induced activation).

PF-5274857 is a potent, orally active and selective inhibitor of hedgehog (Hh) signaling pathway (IC50 = 5.8 nM, Ki = 4.6 nM) . PF-5274857 effectively penetrates the blood-brain barrier and inhibits Smo activity in the brain of primary medulloblastoma mic

Ciliobrevin A (HPI-4) is an inhibitor of the hedgehog signaling pathway with an IC50 of less than 10 μM.

HPI-1 (hydrate) is a Hedgehog (Hh) pathway inhibitor that suppresses signaling through Sonic Hh (IC50= 1.5 μM) without significantly affecting Wnt signaling (IC50≥ 30 μM).1HPI-1 suppresses Hh activation induced by loss of Suppressor of Fused or by Gli overexpression, suggesting action at posttranslational modification of Gli protein or at the interaction of Gli with a co-factor.1HPI-1 (hydrate) also inhibits signaling through the oncogenic Smoothened (Smo) mutant SmoM2 in neuron precursors, preventing cell proliferation.1 1.Hyman, J.M., Firestone, A.J., Heine, V.M., et al.Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockadeProceedings of the National Academy of Sciences of the United States of America106(33)14132-14137(2009)

JK184, a potent Hedgehog (Hh) pathway inhibitor.

Saponin activator. Activates release of Prostaglandin E2 in vitro. Anti-inflammatory agent. Orally active. Active in vivo and in vitro.

PF-5274857 (PF-5274857 free base) is an effective and selective hedgehog signaling pathway inhibitor (IC50: 5.8 nM and a Ki: 4.6 nM). PF-5274857 is a potentially attractive clinical candidate for the treatment of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway.PF-5274857 was found to effectively penetrate the blood-brain barrier and inhibit Smo activity in the brain of primary medulloblastoma mice, resulting in improved animal survival rates. PF-5274857 was orally available and metabolically stable in vivo.

SMO-IN-3 is a potent inhibitor of smoothened (SMO) that acts on the hedgehog (Hh) signaling pathway (IC50: 34.09 nM). SMO-IN-3 inhibits the proliferation of Daoy, a human medulloblastoma cell line, and exhibits anticancer effects.

MK-4101, an effective inhibitor of the Hedgehog pathway, has anti-tumor activity through the induction of extensive apoptosis and inhibition of proliferation in tumor cells.

NL-103 is a novel dual-targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations. NL-103 comprises structural elements of Hh pathway inhibitor vismodegib, and histone deacetylase (HDAC) inhibitor vorinostat. NL-103 simultaneously and significantly inhibited both HDACs and Hh pathway. Importantly, NL-103 effectively overcame vismodegib resistance induced by Smoothened point mutations. Moreover, NL-103 significantly downregulated the expression of Gli2 which plays an important role in Hh pathway. NL-103 may be a promising compound for clinical development as a more effective Hh pathway inhibitor.

M-25 is a Smoothened antagonist and inhibitor of the Hedgehog pathway.

Patidegip, laos known as Saridegib and IPI-926, is an orally bioavailable, cyclopamine-derived (for structure comparison see Fig 1) inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Specifically, Hedgehog pathway inhibitor IPI-926 binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations.

Glasdegib hydrochloride is a small-molecule inhibitor of the Hedgehog (Hh) signaling pathway with potential antineoplastic activity.

3-epi-Vitamin D3 (Epicholecalciferol), an analogue of Vitamin D3, serves as a Hedgehog pathway inhibitor, exhibiting potency with an IC50 value of 39.2 μM in U87MG cells.